1. Salicylates
Medications containing
salicylates are Alka–Seltzer, Anacin, Aspirin, Bufferin, Excedrin, and Midol.
Salicylates are classified as anti–inflammatory, anti– pyretic analgesics and
are used to reduce inflammation, fever and pain.
Initially,
salicylate toxicity causes respiratory alkalosis because salicylates stimulate the
respiratory center of the CNS, causing hyperapnea, tachypnea. Salicylates also
inhibit enzyme in the Kreb cycle, causing pyruvate to be converted to lactic
acid. Lipid metabolism is increased, amino acid metabolism is decreased and
accumulation of organic acids eventually leads to metabolic acidosis.
Clinical
symptoms of salicylate toxicity include tinnitus, hyperapnea, tachypnea, lethargy,
vomiting and possibly coma, convulsions, and hyperthermia in severe cases.
Severity of the overdose is assessed by arterial blood gas and electrolyte
results. Respiratory alkalosis is apparent in the early stages of toxicity and
metabolic acidosis with an increased anion gap maybe apparent in later stages.
The
determination of salicylates in biological fluid is based on the formation of
violet colored complex between ferric ion and phenol.
2. Acetaminophen
Some common
trade names of acetaminophen include Tylenol, Datril, and Anacin–3. It has an
analgesic and antipyretic properties. An overdose of this drug causes
hepatotoxicity.
Symptoms of toxicity
First 24–48 hours – nausea, vomiting
or anorexia, liver necrosis begins with hepatic enzymes, bilirubin and
prothrombin time.
3–5 days – symptoms resembling that
of viral hepatitis occur.
Acetaminophen, unlike most other drugs
does have a specific antidote that is used in severe overdose cases. N–acetylcysteine
(mucomyst) effectively reduces the amount of liver necrosis by reducing
accumulation of toxic acetaminophen metabolite in the liver. Treatment with N–acetylcysteine
must begin within 10 hours after ingestion to be maximally effective.
****** DRUGS OF ABUSE ******
Classification of drugs of
abuse
1. Depressant
or downers
a. Alcohol
b. Sedative
c. Narcotics
d. Tranquilizers
2. Stimulant
or uppers
a. Cocaine
b. Amphetamine
c. Methampenamine
3. Hallucinogenics
a. Phencyclidine
b. Lysergic
Acid Diethylamide (LSD)
c. Mescaline
****** AMPHETAMINE
******
Are related chemically and their
physiological effects to the biologically active principle of the adrenal
medulla, namely epinephrine and adrenalin.
John Abel was the first one to
recognize and latter to isolate epinephrine in 1890. In 1920, ephedrine was
obtained from the Chinese herb Ma huang (Ephedra vulgaris).
Ephedrine has a similar action as ephedrine and its effects last longer than
epinephrine. Ephedrine was also used in alleviating the symptoms of asthma.
Since it was difficult to obtain
natural supplies of ephedrine, amphetamine was synthesized by Gordon Alleles
and George Pines in 1927. Like ephedrine, amphetamine has stimulating effect in
the central nervous system. Benzidrine inhaler which is used to reduce nasal
decongestion is a form of amphetamine.
Uses of amphetamine in medicine
1. To
keep the patient awake in narcolepsy. Narcolepsy is a disorder characterized by
brief attacks of deep sleeps.
2. To
curb the appetite in overweight persons.
3. To
relieve mild depression such as that accompanying grief, senility, menopause
and convulsions.
4. Use
as stimulant.
In a pure
state, amphetamine is a colorless, volatile liquid with a strong odor and
burning state.
Administration: Injection, oral in the form of tablet or
capsule
Most common amphetamine
stimulant
1. Benzidine
2. Dexedrine
3. Methedrine
When taken occasionally, the effects
on the person are:
1. Exhiliration
2. Peppiness
3. Increase
capacity for thinking
Often called “pep pills” or “jolly
beavers,” when one exceeds the prescribed doses, the drug is supposed to be
abused. Over dosages produce the following effects:
1. Excitability
2. Unclear
or rapid speech
3. Restlessness
4. Tremors
of the hand
5. Dilated
pupil
6. Sleeplessness
7. Profused
perspiration
Hearing or visual hallucination or
both may be noted especially when excessive daily doses have been taken for a
long time.
Most severe complication of excessive
use of amphetamine is psychoses, usually of the paranoid type. Amphetamine does
not react to yield crystal on precipitate with Wagner, Mayer, Marme or picric
acid reagent.
Amphetamine base and benzidine sulfate
each give color reaction with various alkaloidal reagents. Place a small
aliquot portion of residue into various grooves of a spot plate. Add to each
groove one of the following reagents and note color produced.
Salt
Base
1. Sulfuric
acid red brown green yellow
2. Mandeline
reagent brick red
3. Sulfuric
acid plus
Vanillin brown red
4. Froede
reagent red
5. Marquis
reagent orange red brown
****** LYSERGIC ACID DIETHYLAMIDE (LSD–25 DELYSID) *****
Synthesized by Stoll and Hoffman from
the basic radical or ergot alkaloids. Hallucinogenic properties were discovered
when they accidentally inhaled the powder.
Toxic dose I.V. LD50 for rat is
65 mg/ kg
–
toxic dose in human has not been determined
–
symptoms can be seen after ingesting 20 mg.
–
a dose of 1500 ug has been tolerated without fatality
Symptoms and actions:
1. Hallucination
of form, color, time and space are produced.
2. Often
with depersonalization of the subject so that he seems to observing himself
from a distance.
3. Restlessness,
vertigo, nausea and vomiting.
4. Increase
body temperature
5. Vascular
hypotension
6. Increased
rate of breathing and parasthesias
7. Atropine
like effects like dilatation of the pupils and dryness of the mouth
8. LDS
is a potent antagonist of 5–hydroxytryptamine.
Distribution in brain
1. In
the brain of monkey, it is localized in area concerned with peripheral
integration and emotional reaction.
2. Concentration
is low in the neocortex which controls simple perception, locomotion and
reasoning.
3. Concentration
is three times as high in the hypothalamus, limbic cortex and in the auditory
and visual reflex centers.
Fate and excretion
The drug is oxidized to 2–oxyl–LSD in
the liver and excreted in the bile. Very little is found in the urine.
****** MARIJUANA (CANNABIS SATIVA) ******
Derived from the plant, “Hemp.” Hemp
originated in the Himalayan Mountains of Asia was used by the Chinese in the
manufacture of ropes and textiles.
The flowering tops of the female plant
when carefully cultivated yield a highly potent intoxicating resin. The male plant
does not secrete any resin. The male plant does not secrete any resin and is
the source of raw materials for the manufacture of linseed oil substitutes and
of fibers for the textiles and ropes.
Tetrahydrocannabinol (THC) is the
chemical responsible for the intoxicating properties of hemp.
Symptoms of toxicity
1. Acts
as descending depressants with generalized depression of the reticular
formation and the primary pathways.
2. Dissociation
and disorientation of personality are more frequent
3. Euphoria,
emotional excitement, uncontrolled laughter, hallucination and illusion
4. Great
distortion of the sense of time and space.
5. Increase
sensitivity to sound and feeling.
6. Acts
of violence due to ideas of persecution are common.
7. Amorous
tendencies are described.
Duration of poisoning
Because THC is lipid soluble, it has
tendency to accumulate in body fat where it has a half–life of 7–8 days.
Chronic use at intervals less than the half–life results in large amounts of
THC being stored in fatty tissue. THC may remain detectable in urine for
several days to 1 week after a single exposure. In a heavy long term user, THC
that has accumulated in fatty tissue is gradually released into the circulation
and it may remain detectable for 21–30 days after the last dose.
****** PHENCYCLIDINE (PCP) ******
It causes hallucination but may also
act as both CNS stimulant and depressant. PCP was originally developed as a
short–acting analgesic for humans and later used as a veterinary anesthetic.
A person who has taken PCP may exhibit
depressant, stimulant or hallucinogenic patterns depending on dosage and route
of administration. At low doses, the user may experience euphoria. Overdoses
may cause the user to have a sense of superhuman strength and may also lead to
coma.
Other symptoms of PCP overdose include
generalized muscle rigidity, seizure, tachycardia and hypertension.
******* OPIATES
******
Symptoms of opiate use include CNS
depression, shallow respirations with a slow respiratory rate, pin point pupils
and hypothermia. The opiates are one of the minority of drugs or drug groups
that have a specific antidote.
Patients who are suspected of
ingesting an overdose of any of the opiates are treated with naloxone (Narcan).
Naloxone is a specific opiate antagonist that reverses CNS depression within 1
to 3 minutes. Because it has no significant side effects, naloxone may be used
both diagnostically and therapeutically. Naloxone is given to a patient who exhibit
signs of narcotic overdose before results of a drug screen known. If the
patient’s symptom improves, then one of the opiates is assumed to be the cause;
if there is no improvement, opiates can be ruled out. Naloxone can also be used
in treating patient with propoxylene toxicity.
CONCEPT OF A
PSEUDOCHOLINESTERASE ACTIVITY
Pseudocholinesterase (ChE) activity in
serum probably represents a group of 11 or more enzymes that are capable of
hydrolyzing several choline esters other than acetylcholine (e.g.,
benzoxylcholine, butyrylthiocholine) and are reduced in activity after
pesticide exposure. The physiologic role of these enzymes is not known, but
their activities in serum are decreased after acute exposure to organophosphate
and carbamate pesticides. Activities are also decreased in liver disease,
chronic alcoholism and malnutrition and in patients with inherited forms of ChE
that have decreased activity.
Methods for measurement of serum ChE
activity are usually based on hydrolysis of synthetic substrate, a thiocholine
ester, to release thiocholine, which then reacts with a color reagent to
produce a color product that absorbs at 405 – 410 nm. This method has been
automated for the DuPont ACA and several manual methods are available in kit
forms.
Serum ChE activity may be lowered by
exposure to levels of pesticides less than those necessary to produce clinical
symptoms and may thus be considered a sensitive indicator of pesticide
exposure. ChE may be decreased within 24 hours after exposure and decreases may
persist for several weeks.
Laboratory diagnosis of
poisoning
1.
Screening
methods
a.
Spot test and
color reactions
– reagents are added to an aliquot of the specimen and a colored complex is
formed in the presence of a particular drug.
(1) Used
for
Acetaminophen
Imipramine
Salicylates
Phenothiazines
(2) Advantages
No
sample pre–treatment
Rapid
and inexpensive
Require
little technical expertise
(3) Disadvantages
Less
sensitive and specific
b.
Immunoassays – a drug
present in a patient specimen competes with a labeled drug for a limited number
of binding sites on antibodies that are specific for the drug being measured.
(1) Radioimmunoassay
(2) Enzyme–multiplied
immunoassay technique (EMIT)
(3) Fluorescence
polarization immunoassay (FPIA)
Advantages
(1) RIA
is the most sensitive but require long incubation period and are not suitable
for drug screening in emergency situation
(2) EMIT
and FPIA requires no sample pre–treatment, are sensitive in the microgram to
nanogram per milliliter range. Provide the rapid turn around time suitable for
emergency situation, and have been adapted for use on automated instruments.
Disadvantages
(1) Each
immunoassay test is specific for one drug or drug group and test are not
available for every drug.
(2) Some
immunoassays cross–react with other structurally similar drugs or drug
metabolite.
c.
Thin layer
Chromatography
2.
Confirmatory
methods
a. Gas
Liquid Chromatography
b. High
Performance Liquid Chromatography (HPLC)
c. Gas
Chromatography–Mass Spectrophotometry
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